The Epstein Barr virus (EBV) is an oncogenic herpesvirus that is intimately involved in a number of malignancies in humans. The genetic basis of EBV associated oncogenesis is the concerted action of EBV latency associated genes and varying cellular genetic alterations. In immuno-competent individuals only minimal EBV latency gene expression can be tolerated due to the immunogeneticity of several EBV encoded latency gene products. In AIDS patients, however, expression of the full repertoire of latency genes (referred to as type III latency) can sometimes be tolerated and expression of these genes provide many essential elements of tumor cell development. In this setting, fewer cellular genetic alterations are required to give rise to malignant cell populations and this probably partly explains the greatly increased susceptibility of AIDS patients to EBV associated non-Hodgkin's lymphomas. The cellular microRNA, miR-155, is one of the most highly implicated microRNAs in cancer. miR-155 is induced by the EBV type III latency program (but not the type I latency program) suggesting a possible role for miR-155 in modulating type III latency signal transduction. Further evidence that miR-155 signaling is relevant to herpesvirus biology has been provided by Rolf Renne's lab and by Bryan Cullen's lab who both showed recently that the Kaposi's Sarcoma Herpes virus (KSHV) encodes a functional homologue of miR- 155. Two mouse miR-155 knock out papers recently showed that miR-155 is important for B cell activation responses following immune challenge. We hypothesize that induction of miR-155 by EBV type III latency plays a role in facilitating EBV mediated B cell activation and that miR-155 modulates signal transduction pathways that contribute to EBV associated maligancies in AIDS patients.

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EBV is associated with a number of human cancers including nasopharyngeal carcinoma, Hodgkin's lymphoma, Burkitt's lymphoma as well as a number of B-cell lymphomas in AIDS patients. Our studies are aimed at addressing the role of an oncogenic cellular microRNA, miR-155, that is induced by EBV latency genes expressed in AIDS associated malignancies.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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Special Emphasis Panel (ZRG1-AARR-H (02))
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Daschner, Phillip J
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Tulane University
Schools of Medicine
New Orleans
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Lin, Zhen; Swan, Kenneth; Zhang, Xin et al. (2016) Secreted Oral Epithelial Cell Membrane Vesicles Induce Epstein-Barr Virus Reactivation in Latently Infected B Cells. J Virol 90:3469-79
Cao, Subing; Moss, Walter; O'Grady, Tina et al. (2015) New Noncoding Lytic Transcripts Derived from the Epstein-Barr Virus Latency Origin of Replication, oriP, Are Hyperedited, Bind the Paraspeckle Protein, NONO/p54nrb, and Support Viral Lytic Transcription. J Virol 89:7120-32
Cao, Subing; Strong, Michael J; Wang, Xia et al. (2015) High-throughput RNA sequencing-based virome analysis of 50 lymphoma cell lines from the Cancer Cell Line Encyclopedia project. J Virol 89:713-29
Strong, Michael J; Xu, Guorong; Morici, Lisa et al. (2014) Microbial contamination in next generation sequencing: implications for sequence-based analysis of clinical samples. PLoS Pathog 10:e1004437
O'Grady, Tina; Cao, Subing; Strong, Michael J et al. (2014) Global bidirectional transcription of the Epstein-Barr virus genome during reactivation. J Virol 88:1604-16
Xu, Guorong; Strong, Michael J; Lacey, Michelle R et al. (2014) RNA CoMPASS: a dual approach for pathogen and host transcriptome analysis of RNA-seq datasets. PLoS One 9:e89445
Martin, Elizabeth C; Elliott, Steven; Rhodes, Lyndsay V et al. (2014) Preferential star strand biogenesis of pre-miR-24-2 targets PKC-alpha and suppresses cell survival in MCF-7 breast cancer cells. Mol Carcinog 53:38-48
Strong, Michael J; Lin, Zhen; Flemington, Erik K (2014) Expanding the conversation on high-throughput virome sequencing standards to include consideration of microbial contamination sources. MBio 5:e01989
Striker, Rob; Mehle, Andrew (2014) Inhibitors of peptidyl proline isomerases as antivirals in hepatitis C and other viruses. PLoS Pathog 10:e1004428
Martin, Elizabeth C; Rhodes, Lyndsay V; Elliott, Steven et al. (2014) microRNA regulation of mammalian target of rapamycin expression and activity controls estrogen receptor function and RAD001 sensitivity. Mol Cancer 13:229

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